Junqueira-Ayres Décio D, Asth Laila, Ayres Adriana S F S J, Lobão-Soares Bruno, Soares-Rachetti Vanessa de Paula, Gavioli Elaine C
Behavioral Pharmacology Laboratory, Department of Biophysics and Pharmacology, Federal University of Rio Grande do Norte.
Exp Clin Psychopharmacol. 2017 Apr;25(2):105-113. doi: 10.1037/pha0000118. Epub 2017 Mar 13.
Anxiety disorders are associated with increased impairments in psychosocial functioning, work productivity and health-related quality of life. In addition, anxiety is a common symptom of ethanol withdrawal and it strongly contributes to relapse. Benzodiazepines are frequently prescribed for relief of anxiety and ethanol withdrawal symptoms but considerable side effects, such sedation, tolerance and dependence, are observed during treatment. Therefore, better drugs are needed for the treatment of anxiety states. The purpose of this study was to investigate whether topiramate would reduce basal levels of anxiety and ethanol-withdrawn induced anxiety in male rats; the elevated plus maze (EPM) was used as an animal model of anxiety. In Experiment 1, topiramate (0, 10, and 40 mg/kg, i.g.) and diazepam (1 mg/kg, i.p.) was acutely and repeatedly administered to naive rats. In Experiments 2 and 3, topiramate (0 or 40 mg/kg, i.g.) was acutely and chronically administered in early (72 hr after ethanol removal) and protracted (21 days after ethanol removal) ethanol-withdrawn rats, respectively. Acute and repeated topiramate treatment induced anxiolytic-like effects in naive rats. Early ethanol withdrawal increased anxiety, and acute topiramate administration counteracted the anxiogenic-like effects of ethanol removal. Protracted withdrawal did not produce lasting changes in anxiety but topiramate was equally effective at reducing anxiety in ethanol-withdrawn and control animals. Importantly, no signs of tolerance to the anxiolytic effects of topiramate were observed. In conclusion, these data support a role for topiramate in the treatment of basal levels of anxiety and ethanol withdrawal-induced anxiety. (PsycINFO Database Record
焦虑症与心理社会功能、工作效率及健康相关生活质量的损害增加有关。此外，焦虑是乙醇戒断的常见症状，且对复发有很大影响。苯二氮䓬类药物常用于缓解焦虑和乙醇戒断症状，但在治疗期间会观察到相当多的副作用，如镇静、耐受性和依赖性。因此，治疗焦虑状态需要更好的药物。本研究的目的是调查托吡酯是否会降低雄性大鼠的基础焦虑水平以及乙醇戒断诱导的焦虑；高架十字迷宫（EPM）被用作焦虑的动物模型。在实验1中，对未处理的大鼠急性重复给予托吡酯（0、10和40mg/kg，腹腔注射）和地西泮（1mg/kg，腹腔注射）。在实验2和3中，分别对早期（乙醇戒断72小时后）和长期（乙醇戒断21天后）乙醇戒断的大鼠急性和慢性给予托吡酯（0或40mg/kg，腹腔注射）。急性重复给予托吡酯对未处理的大鼠产生抗焦虑样作用。早期乙醇戒断增加焦虑，急性给予托吡酯可抵消乙醇戒断的致焦虑样作用。长期戒断未产生焦虑的持久变化，但托吡酯在降低乙醇戒断动物和对照动物的焦虑方面同样有效。重要的是，未观察到对托吡酯抗焦虑作用产生耐受性的迹象。总之，这些数据支持托吡酯在治疗基础焦虑水平和乙醇戒断诱导的焦虑中的作用。（PsycINFO数据库记录）
